Pharmacokinetics of the levonorgestrel-only emergency contraception regimen in normal-weight, obese, and extremely obese users: A pilot study
Contraception
Awarded 2012
Large Research Grants
Melissa Natavio, MD, MPH
University of Southern California
$120,000

Objective: To determine if differences exist in the pharmacokinetics of levonorgestrel-only emergency contraception (LNG-EC) in normal, obese and extremely obese users. Methods: Healthy, reproductive-age, ovulatory women with normal (BMI 18.5-24.9 kg/m2), obese (BMI = 30-39.9 kg/m2) and extremely obese (BMI >= 40 kg/m2) BMIs were orally administered 1.5 mg LNG-EC. Dosing occurred on day 8 of their menstrual cycle. LNG PK parameters were obtained via serum samples through a venous catheter at 0, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 and 96 hours after LNG-EC administration. The primary outcome is to compare the maximum concentration (Cmax), time to maximum concentration (Tmax), area under the curve (AUC) of LNG in normal-weight, obese and extremely obese users. Results: The study is ongoing. To date, 23 of 30 women have enrolled in the study. We have complete data analysis for 18 participants (normal BMI = 8, median 22.7, range 18.5-24.9, obese BMI = 6, median 34.6, range 30.2-37.2, extremely obese = 3, median 45.1, range 40.5 – 55.2). With the exception of BMI there were no notable differences in the baseline demographic characteristics between the three BMI groups. Tmax was similar between BMI category (medians: 2, 2.5, 2 hrs). Compared to normal BMI subjects total LNG Cmax for obese subjects was lower (11.4 versus 15 ng/ml). For extremely obese subjects the Cmax was the lowest of the three groups (9.44 ng/ml). The calculated AUC total showed similar results. The AUC for extremely obese subjects (164.4 ± 14.1 ng/ml/hr) was lower than the level observed in obese (186.3 ± 51.2) and normal BMI women (347.2 ± 121.4). Obesity also impacted the t1/2 for LNG, which was almost double (50.6 ± 7.4 h for obese and 48.1 ± 1.5 h for extremely obese) that of normal BMI subjects (30.1 ± 10.2 h). A longer t½ translates into a longer time to achieve steady-state levels of LNG. Conclusion and Clinical Implications: Preliminary results show obesity appears to impact LNG Cmax levels, t 1/2, AUC without impacting Tmax. Final data analysis is pending of the remaining participants pK and effects on ovarian activity/ovulation suppression.

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